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Mar. 7, 2013 — Nanoparticles carrying a toxin found in bee venom can destroy human immunodeficiency virus (HIV) while leaving surrounding cells unharmed, researchers at Washington University School of Medicine in St. Louis have shown. The finding is an important step toward developing a vaginal gel that may prevent the spread of HIV, the virus that causes AIDS.

"Our hope is that in places where HIV is running rampant, people could use this gel as a preventive measure to stop the initial infection," says Joshua L. Hood, MD, PhD, a research instructor in medicine. The study appears in the current issue of Antiviral Therapy.

Bee venom contains a potent toxin called melittin that can poke holes in the protective envelope that surrounds HIV, and other viruses. Large amounts of free melittin can cause a lot of damage. Indeed, in addition to anti-viral therapy, the paper's senior author, Samuel A. Wickline, MD, the J. Russell Hornsby Professor of Biomedical Sciences, has shown melittin-loaded nanoparticles to be effective in killing tumor cells.

The new study shows that melittin loaded onto these nanoparticles does not harm normal cells. That's because Hood added protective bumpers to the nanoparticle surface. When the nanoparticles come into contact with normal cells, which are much larger in size, the particles simply bounce off. HIV, on the other hand, is even smaller than the nanoparticle, so HIV fits between the bumpers and makes contact with the surface of the nanoparticle, where the bee toxin awaits.

"Melittin on the nanoparticles fuses with the viral envelope," Hood says. "The melittin forms little pore-like attack complexes and ruptures the envelope, stripping it off the virus."

According to Hood, an advantage of this approach is that the nanoparticle attacks an essential part of the virus' structure. In contrast, most anti-HIV drugs inhibit the virus's ability to replicate. But this anti-replication strategy does nothing to stop initial infection, and some strains of the virus have found ways around these drugs and reproduce anyway.

"We are attacking an inherent physical property of HIV," Hood says. "Theoretically, there isn't any way for the virus to adapt to that. The virus has to have a protective coat, a double-layered membrane that covers the virus."Beyond prevention in the form of a vaginal gel, Hood also sees potential for using nanoparticles with melittin as therapy for existing HIV infections, especially those that are drug-resistant. The nanoparticles could be injected intravenously and, in theory, would be able to clear HIV from the blood stream.

"The basic particle that we are using in these experiments was developed many years ago as an artificial blood product," Hood says. "It didn't work very well for delivering oxygen, but it circulates safely in the body and gives us a nice platform that we can adapt to fight different kinds of infections."

Since melittin attacks double-layered membranes indiscriminately, this concept is not limited to HIV. Many viruses, including hepatitis B and C, rely on the same kind of protective envelope and would be vulnerable to melittin-loaded nanoparticles.While this particular paper does not address contraception, Hood says the gel easily could be adapted to target sperm as well as HIV. But in some cases people may only want the HIV protection.

"We also are looking at this for couples where only one of the partners has HIV, and they want to have a baby," Hood says. "These particles by themselves are actually very safe for sperm, for the same reason they are safe for vaginal cells."While this work was done in cells in a laboratory environment, Hood and his colleagues say the nanoparticles are easy to manufacture in large enough quantities to supply them for future clinical trials.

This work was supported by the Bill & Melinda Gates Foundation Grand Challenges Explorations grant number OPP1024642 'Fusogenic nanoparticles for combined anti-HIV/contraception.'

I like how they only use the term vaginal gel when discussing potential uses. I guess online science news sites aren't ready to discuss anal lubes yet.

While I fully understand and empathise with how the focus on a vaginal-lube (microbial gel) preventative may rankle with gay men, please try to understand the issue from a global viewpoint.

Globally, hiv affects more women than men in resource-poor places like parts of Asia and Africa. Often times women are powerless to insist their men use condoms and are often beaten and/or abandoned if they do try to insist on condoms.

A microbial gel that can be inserted into the vagina (without the man's knowledge) would save so much pain and heartache (not to mention hiv infections) in the developing world.

While the developed world still tends to think of hiv as a disease of gay men, there are more women world-wide than men who are living with hiv. And a lot of that is a direct result of the poverty and powerless of women in third-world countries.

The focus on preventing vaginal (man to woman) transmission is also indirectly a focus on preventing transmission from mother to child. It's a very large picture overall.

But do not despair as a gay man - this focus is going to ultimately ALSO benefit gay men. It's just that in this particular field of hiv prevention research, the focus is (for once), on women and that's how it should be. The reason I ask you to not despair nor feel slighted is because once we find a microbial gel that works vaginally for women, there is no reason to think that it won't work for MSM as well.

Historically, research into any of the various fields of hiv treatment and prevention has by and large been conducted on men. So please don't begrudge this one small area where the focus has been on women. At the end of the day, it will benefit us all.

It's not so much that online news sites are reluctant (or squeamish or whatever) to report the development of microbial gels from the anal point of view, it's simply that the research itself is focusing on vaginal use. Once we have a microbial gel that works vaginally, as I said earlier, there's no reason to think it won't work rectally as well.

It's just that there is a greater need for a vaginal gel, due in large part to gender politics and the powerlessness of women to negotiate for condom use in many cultures - those same cultures where hiv is rampant amongst the heterosexual community.

I'm not so sure that this sort of thing would be used as an under-the-skin implant. The agents they've been looking at for use in antimicrobial gels are agents that protect the cells that hiv can latch onto and infect, such as the cells that line the vagina. These same types of cells are also found in the rectum.

It makes more sense to deliver these antimicrobial agents directly to the area where they're needed, rather than some under-the-skin implant, unless of course if you're suggesting these implants are placed inside the vagina or rectum. I can't see that happening.

Any advance in a viable antimicrobial vaginal gel is good news, because any such gel is very likely - if not most certainly - going to work in the rectal tissues as well. So rather than feel slighted that you rarely see reference to an anal application when reading these news stories, rejoice that we've come another step closer to producing something like this that works, because it will work for women and men alike. It just so happens that women have the greater need at the moment - not only for their own sakes, but also for their (unborn) children's sake as well.

"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

Nymphomaniac: a woman as obsessed with sex as an average man. Mignon McLaughlin

HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

Quite a nice summary, Ann. I totally agree and don't feel slighted. I just had a bit of a chuckle when I read the story because even when talking about topic which so many people find a taboo topic (HIV), the writer kept away from the other taboo topic of inserting things into an anus. The way I see HIV research is that one small step forwards for one part of the population ultimately will lead to huge gains for everyone just because we know so little.

The nano particle technology was initially developed to be injected into the blood stream. My mind immediately went to a future of everyone having nanoparticles in their blood acting as almost a secondary immune system. If this technology works it has much bigger implications than just HIV.

But do not despair as a gay man - this focus is going to ultimately ALSO benefit gay men. It's just that in this particular field of hiv prevention research, the focus is (for once), on women and that's how it should be. The reason I ask you to not despair nor feel slighted is because once we find a microbial gel that works vaginally for women, there is no reason to think that it won't work for MSM as well.

I wonder how much of Anal sex transmission is due to blood-to-blood contact (both skins rupture) and how much of it is due to semen-to-blood contact (only the bottom's skin rupture). If you are more likely to get the virus because two skins ruptured and there was blood contact, then a gel would just be as ineffective as on the arms of intravenous drug users sharing needles.

The application of this gel will be topical: it's applied on the outside of the skin.These nanoparticles discussed here are very large. They have openings through which the virus can enter the nanoparticle. Such a large particle cannot cross a cell membrane (unlike let's say a drug, which are usually very small molecules). Therefore, when applied to the skin it will not enter the blood stream.

Out of curiosity, how would this affect those who have an allergic reaction to bee stings?

None, for several reasons. One being, that as I wrote above, these nanoparticles will not enter the body.

Quote from: YellowFever

I wonder how much of Anal sex transmission is due to blood-to-blood contact (both skins rupture) and how much of it is due to semen-to-blood contact (only the bottom's skin rupture).

I've been wondering that too! Well, the transmission risk is much lower when there is no ejaculation. This points to semen-to-blood transmission. On the other hand also a Top can get infected.One thing that I find rather confusing is the role of anal mucus. Sometimes it's not being mentioned at all and only semen and blood are being discussed. And other times I hear that the viral load of the anal mucus is even higher than in blood and that it's particularly dangerous. (here is one example).

I wonder how much of Anal sex transmission is due to blood-to-blood contact (both skins rupture) and how much of it is due to semen-to-blood contact (only the bottom's skin rupture). If you are more likely to get the virus because two skins ruptured and there was blood contact, then a gel would just be as ineffective as on the arms of intravenous drug users sharing needles.

"The risk of becoming infected with HIV during unprotected anal sex is 10 to 20 times greater than unprotected vaginal sex. Because the rectal lining is only one-cell thick, the virus can more easily reach immune cells to infect."